Nordentatin Inhibits Neuroblastoma Cell Proliferation and Migration through Regulation of GSK-3 Pathway

Boonyarat, Chantana; Boonput, Panatchakorn; Tongloh, Nantakorn; Kaewamatawong, Rawiwun; Chaiwiwatrakul, Suchada; Yenjai, Chavi; Waiwut, Pornthip

doi:10.3390/cimb44030070

Cited by 5 publications

(4 citation statements)

References 42 publications

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“…The root bark of CH has been reported to contain a number of coumarins and carbazoles [ 21 , 22 , 23 , 24 , 25 ]. We standardized the root-bark extract of CH by using three coumarins and four carbazoles [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…The crude extracts of CH have been reported to exert anti-inflammatory and antioxidant effects in evaluations of their biological activities [ 20 ]. Phytochemical investigations have revealed that CH contains a number of carbazole alkaloids and coumarins [ 21 , 22 , 23 , 24 , 25 ]. Several studies have illustrated that coumarins show a wide range of biological activities relevant to AD including antioxidant effects and the inhibition of Aβ aggregation [ 26 ], AChE function [ 27 ], and iNOS protein expression [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

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Multifunctionality of Clausena harmandiana Extract and Its Active Constituents against Alzheimer’s Disease

Boonyarat

Yenjai

Monthakantirat

et al. 2022

CIMB

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This study was designed to investigate the effects of the root-bark extract of Clausena harmandiana (CH) and its active constituents (nordentatin and 7-methoxyheptaphylline) on pharmacological activities regarding selected targets associated with AD, namely, its antioxidant activity, inhibition of Aβ aggregation, acetylcholinesterase (AChE) activity, and neuroprotective effects. The effect of the CH extract on the cognitive impairment induced by scopolamine was also evaluated in mice. The effects of the CH extract and its active constituents on radical scavenging, Aβ aggregation, and AChE activity were investigated with a 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) assay, a thioflavin-T assay, and Ellman’s method. The neuroprotective effects of the extract against hydrogen-peroxide and Aβ toxicity were evaluated with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. In addition, the effects on cognitive impairment induced by scopolamine in mice were evaluated using Morris-water-maze and modified-Y-maze test models. The results of the present study demonstrate that the root-bark extract of CH shows multimodal actions relevant to the AD pathological cascade, including antioxidant effects, the inhibition of Aβ aggregation, the inhibition of AChE function, and neuroprotection against oxidative stress and Aβ toxicity. The extracts could improve both the short- and long-term memory deficits induced by scopolamine in mice.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multifunctionality of Clausena harmandiana Extract and Its Active Constituents against Alzheimer’s Disease

Boonyarat

Yenjai

Monthakantirat

et al. 2022

CIMB

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“…A reduction in Mcl-1 concentration results in Bax activation. This leads to caspase-3 cleavage and the inhibition of the migratory protein MMP-9 via the glycogen synthase kinase-3 (GSK-3) pathway, ultimately inhibiting the proliferation and migration of NB cells [ 63 ].…”

Section: Mechanisms Of Apoptotic Actionmentioning

confidence: 99%

Potential Treatment Options for Neuroblastoma with Polyphenols through Anti-Proliferative and Apoptotic Mechanisms

et al. 2023

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Neuroblastoma (NB) is an extracranial tumor of the peripheral nervous system arising from neural crest cells. It is the most common malignancy in infants and the most common extracranial solid tumor in children. The current treatment for high-risk NB involves chemotherapy and surgical resection followed by high-dose chemotherapy with autologous stem-cell rescue and radiation treatment. However, those with high-risk NB are susceptible to relapse and the long-term side effects of standard chemotherapy. Polyphenols, including the sub-class of flavonoids, contain more than one aromatic ring with hydroxyl groups. The literature demonstrates their utility in inducing the apoptosis of neuroblastoma cells, mostly in vitro and some in vivo. This review explores the use of various polyphenols outlined in primary studies, underlines the pathways involved in apoptotic activity, and discusses the dosage and delivery of these polyphenols. Primary studies were obtained from multiple databases with search the terms “neuroblastoma”, “flavonoid”, and “apoptosis”. The in vitro studies showed that polyphenols exert an apoptotic effect on several NB cell lines. These polyphenols include apigenin, genistein, didymin, rutin, quercetin, curcumin, resveratrol, butein, bisphenols, and various plant extracts. The mechanisms of the therapeutic effects include calpain-dependent pathways, receptor-mediated apoptosis, and, notably, and most frequently, mitochondrial apoptosis pathways, including the mitochondrial proteins Bax and Bcl-2. Overall, polyphenols demonstrate potency in decreasing NB proliferation and inducing apoptosis, indicating significant potential for further in vivo research.

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“…Furthermore, sulforaphane blocks the angiogenesis of colon cancer cells by down-regulating HIF1A and VEGF expression [ 487 ]. Nordentatin, an Enkleia siamensis -derived natural product, suppresses the migration of neuroblastoma cells by down-regulating GSK3 expression [ 494 ].…”

Section: Natural Products Regulate Akt Effectors-modulated Cell Funct...mentioning

confidence: 99%

The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products

et al. 2022

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Oxidative stress and AKT serine-threonine kinase (AKT) are responsible for regulating several cell functions of cancer cells. Several natural products modulate both oxidative stress and AKT for anticancer effects. However, the impact of natural product-modulating oxidative stress and AKT on cell functions lacks systemic understanding. Notably, the contribution of regulating cell functions by AKT downstream effectors is not yet well integrated. This review explores the role of oxidative stress and AKT pathway (AKT/AKT effectors) on ten cell functions, including apoptosis, autophagy, endoplasmic reticulum stress, mitochondrial morphogenesis, ferroptosis, necroptosis, DNA damage response, senescence, migration, and cell-cycle progression. The impact of oxidative stress and AKT are connected to these cell functions through cell function mediators. Moreover, the AKT effectors related to cell functions are integrated. Based on this rationale, natural products with the modulating abilities for oxidative stress and AKT pathway exhibit the potential to regulate these cell functions, but some were rarely reported, particularly for AKT effectors. This review sheds light on understanding the roles of oxidative stress and AKT pathway in regulating cell functions, providing future directions for natural products in cancer treatment.

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Nordentatin Inhibits Neuroblastoma Cell Proliferation and Migration through Regulation of GSK-3 Pathway

Cited by 5 publications

References 42 publications

Multifunctionality of Clausena harmandiana Extract and Its Active Constituents against Alzheimer’s Disease

Multifunctionality of Clausena harmandiana Extract and Its Active Constituents against Alzheimer’s Disease

Potential Treatment Options for Neuroblastoma with Polyphenols through Anti-Proliferative and Apoptotic Mechanisms

The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products

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